Trial Outcomes & Findings for Lithium for Suicidal Behavior in Mood Disorders (NCT NCT01928446)

NCT ID: NCT01928446

Last Updated: 2024-04-29

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2/PHASE3

Target enrollment

519 participants

Primary outcome timeframe

1 year

Results posted on

2024-04-29

Participant Flow

1. Assessed for eligibility (n=21887). 2. Signed 1st consent (n=722); * Excluded: did not meet inclusion criteria (n= 173). 3. Signed 2nd consent (n=599); * Excluded: * not randomized (n=78); * assigned to treatment arm, but dropped out prior to receiving Study Meds (n=2).

Participant milestones

Participant milestones
Measure	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 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
Overall Study STARTED	255	264
Overall Study COMPLETED	144	125
Overall Study NOT COMPLETED	111	139

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Lithium for Suicidal Behavior in Mood Disorders

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lithium n=255 Participants 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 n=264 Participants 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	Total n=519 Participants Total of all reporting groups
Age, Continuous	43.2 years STANDARD_DEVIATION 12.4 • n=5 Participants	42.4 years STANDARD_DEVIATION 12.4 • n=7 Participants	42.8 years STANDARD_DEVIATION 12.4 • n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	39 Participants n=7 Participants	82 Participants n=5 Participants
Sex: Female, Male Male	212 Participants n=5 Participants	225 Participants n=7 Participants	437 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	35 Participants n=5 Participants	42 Participants n=7 Participants	77 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	220 Participants n=5 Participants	217 Participants n=7 Participants	437 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Black or African American	39 Participants n=5 Participants	44 Participants n=7 Participants	83 Participants n=5 Participants
Race (NIH/OMB) White	185 Participants n=5 Participants	192 Participants n=7 Participants	377 Participants n=5 Participants
Race (NIH/OMB) More than one race	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	12 Participants n=7 Participants	20 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year

Outcome measures

Outcome measures
Measure	Lithium n=255 Participants 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 n=264 Participants 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
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.	0.0382 Monthly Hazard rate	0.0348 Monthly Hazard rate

PRIMARY outcome

Timeframe: 1 year

Population: Analysis performed for a subset of participants: 88 of 519 subjects took 80% or more of their study medication (46 on lithium, 42 on placebo) and were considered substantially compliant. Twenty of these subjects had primary outcomes (8 on placebo, 12 on lithium).

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.

Outcome measures

Outcome measures
Measure	Lithium n=46 Participants 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 n=42 Participants 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
Number of Compliant Participants With Episode of Self-directed Violence (Per Protocol Analyses)	12 Participants	8 Participants

SECONDARY outcome

Timeframe: 1 year

Subtypes of suicidal self-directed violence: 1. Self-directed violence; 2. Interrupted self-directed violence; 3. Hospitalization to prevent suicide; 4. Death from suicide - there were too few deaths in the study, making data insufficient to perform analysis.

Outcome measures

Outcome measures
Measure	Lithium n=255 Participants 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 n=264 Participants 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
Number of Participants With Subtypes of Suicidal Self-directed Violence for All Recurring Events Other	2 Participants	2 Participants
Number of Participants With Subtypes of Suicidal Self-directed Violence for All Recurring Events Suicidal self-directed violence	11 Participants	10 Participants
Number of Participants With Subtypes of Suicidal Self-directed Violence for All Recurring Events Interrupted suicidal self-directed violence	17 Participants	11 Participants
Number of Participants With Subtypes of Suicidal Self-directed Violence for All Recurring Events Hospitalization to prevent suicide	34 Participants	39 Participants
Number of Participants With Subtypes of Suicidal Self-directed Violence for All Recurring Events Death from suicide	1 Participants	0 Participants

Adverse Events

Lithium

Serious events: 99 serious events

Other events: 193 other events

Deaths: 1 deaths

Placebo

Serious events: 90 serious events

Other events: 166 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Ryan E. Ferguson, ScD, MPH, Director

Boston CSP Coordinating Center

Phone: 1-857-364-4201

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Lithium n=255 participants at risk 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 n=264 participants at risk 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
Gastrointestinal disorders Diarrhoea	22.7% 58/255 • Number of events 70 • Data collected over 395 days from randomization	15.5% 41/264 • Number of events 50 • Data collected over 395 days from randomization
Gastrointestinal disorders Dry mouth	4.7% 12/255 • Number of events 12 • Data collected over 395 days from randomization	5.3% 14/264 • Number of events 14 • Data collected over 395 days from randomization
Gastrointestinal disorders Nausea	15.7% 40/255 • Number of events 48 • Data collected over 395 days from randomization	9.8% 26/264 • Number of events 30 • Data collected over 395 days from randomization
Gastrointestinal disorders Vomiting	5.5% 14/255 • Number of events 15 • Data collected over 395 days from randomization	2.3% 6/264 • Number of events 7 • Data collected over 395 days from randomization
General disorders Fatigue	9.0% 23/255 • Number of events 24 • Data collected over 395 days from randomization	2.7% 7/264 • Number of events 7 • Data collected over 395 days from randomization
General disorders Thirst	11.0% 28/255 • Number of events 33 • Data collected over 395 days from randomization	8.7% 23/264 • Number of events 24 • Data collected over 395 days from randomization
Investigations Electrocardiogram QT prolonged	5.5% 14/255 • Number of events 16 • Data collected over 395 days from randomization	1.9% 5/264 • Number of events 7 • Data collected over 395 days from randomization
Investigations Glomerular filtration rate decreased	13.3% 34/255 • Number of events 41 • Data collected over 395 days from randomization	8.3% 22/264 • Number of events 32 • Data collected over 395 days from randomization
Metabolism and nutrition disorders Decreased appetite	4.7% 12/255 • Number of events 13 • Data collected over 395 days from randomization	5.7% 15/264 • Number of events 15 • Data collected over 395 days from randomization
Metabolism and nutrition disorders Weight fluctuation	3.5% 9/255 • Number of events 10 • Data collected over 395 days from randomization	8.0% 21/264 • Number of events 22 • Data collected over 395 days from randomization
Nervous system disorders Dizziness	9.0% 23/255 • Number of events 26 • Data collected over 395 days from randomization	5.3% 14/264 • Number of events 16 • Data collected over 395 days from randomization
Nervous system disorders Headache	11.8% 30/255 • Number of events 32 • Data collected over 395 days from randomization	12.5% 33/264 • Number of events 35 • Data collected over 395 days from randomization
Nervous system disorders Somnolence	7.1% 18/255 • Number of events 18 • Data collected over 395 days from randomization	11.4% 30/264 • Number of events 35 • Data collected over 395 days from randomization
Nervous system disorders Tremor	23.9% 61/255 • Number of events 72 • Data collected over 395 days from randomization	7.2% 19/264 • Number of events 19 • Data collected over 395 days from randomization
Renal and urinary disorders Pollakiuria	8.6% 22/255 • Number of events 25 • Data collected over 395 days from randomization	8.0% 21/264 • Number of events 23 • Data collected over 395 days from randomization