Trial Outcomes & Findings for Treatment of Psychosis and Agitation in Alzheimer's Disease (NCT NCT02129348)
NCT ID: NCT02129348
Last Updated: 2024-05-02
Results Overview
Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain is the measure used that combines symptoms of agitation and aggression. Frequency X Severity rating score, range 0-12. Minimum score is 0, maximum score is 12. Higher score is a worse outcome and indicates more agitation and aggressive behavior.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
77 participants
Primary outcome timeframe
Assessed at screening, Week 0, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12
Results posted on
2024-05-02
Participant Flow
Participant milestones
| Measure |
Lithium Treatment Group
The patient will be started on lithium 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on lithium blood level. Blood will be drawn at each study visit. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Lithium
|
Placebo Group
The patient will be started on placebo 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on sham lithium blood level. Blood will be drawn for sham lithium levels at weeks 2, 4, 6, 8, and 12. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Placebo
|
|---|---|---|
|
Overall Study
STARTED
|
38
|
39
|
|
Overall Study
COMPLETED
|
29
|
29
|
|
Overall Study
NOT COMPLETED
|
9
|
10
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Treatment of Psychosis and Agitation in Alzheimer's Disease
Baseline characteristics by cohort
| Measure |
Lithium Treatment Group
n=38 Participants
The patient will be started on lithium 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on lithium blood level. Blood will be drawn at each study visit. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Lithium
|
Placebo Group
n=39 Participants
The patient will be started on placebo 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on sham lithium blood level. Blood will be drawn for sham lithium levels at weeks 2, 4, 6, 8, and 12. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Placebo
|
Total
n=77 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
34 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
70 Participants
n=5 Participants
|
|
Age, Continuous
|
75.6 years
STANDARD_DEVIATION 8.3 • n=5 Participants
|
74.3 years
STANDARD_DEVIATION 6.9 • n=7 Participants
|
74.9 years
STANDARD_DEVIATION 7.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
35 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
72 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
33 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
67 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
38 participants
n=5 Participants
|
39 participants
n=7 Participants
|
77 participants
n=5 Participants
|
|
Neuropsychiatric Inventory (NPI) Agitation/Agression Domain
|
7.7 units on a scale
STANDARD_DEVIATION 3.1 • n=5 Participants
|
7.8 units on a scale
STANDARD_DEVIATION 2.9 • n=7 Participants
|
7.75 units on a scale
STANDARD_DEVIATION 3 • n=5 Participants
|
PRIMARY outcome
Timeframe: Assessed at screening, Week 0, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain is the measure used that combines symptoms of agitation and aggression. Frequency X Severity rating score, range 0-12. Minimum score is 0, maximum score is 12. Higher score is a worse outcome and indicates more agitation and aggressive behavior.
Outcome measures
| Measure |
Lithium Treatment Group
n=38 Participants
The patient will be started on lithium 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on lithium blood level. Blood will be drawn at each study visit. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Lithium
|
Placebo Group
n=39 Participants
The patient will be started on placebo 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on sham lithium blood level. Blood will be drawn for sham lithium levels at weeks 2, 4, 6, 8, and 12. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Placebo
|
|---|---|---|
|
Change in Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score
|
3.2 score on a scale
Interval 1.7 to 4.6
|
2.5 score on a scale
Interval 1.1 to 4.0
|
SECONDARY outcome
Timeframe: Week 12The patient is classified as a responder (score=1) if both criteria are met or as a non-responder (score=0) if both criteria are not met. The first criterion to determine responder status, NPI core score, has a scoring range 0-36; each of the three component scores for symptoms of agitation/aggression, delusions and hallucinations has a scoring range 0-12. For each symptom and the total score, higher score indicates more symptoms. The second criterion to determine responder status, Clinical Global Impression (CGI), is used to assess change in overall behavior; scoring range 1-7 with higher scores indicating worsening over time and lower scores indicating improvement over time. Only patients who met both criteria, assessed as change compared to baseline, were counted as responders; all other patients were non-responders. Patients that demonstrated improvement at week 12 were reported; scores for earlier weeks were only used to assess progress throughout the study.
Outcome measures
| Measure |
Lithium Treatment Group
n=38 Participants
The patient will be started on lithium 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on lithium blood level. Blood will be drawn at each study visit. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Lithium
|
Placebo Group
n=39 Participants
The patient will be started on placebo 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on sham lithium blood level. Blood will be drawn for sham lithium levels at weeks 2, 4, 6, 8, and 12. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Placebo
|
|---|---|---|
|
Clinical Responder Defined as a 30% Decrease in NPI Core Score (Sum Score of NPI Domains of Agitation/Aggression, Delusions and Hallucinations) Together With a Clinical Global Impression (CGI) Behavior Change Score of 1 or 2
|
12 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: Week 12Clinical Global Impression (CGI) Behavior Change score is the measure used to assess change in overall behavior; scoring range 1-7 with higher scores indicating worsening over time and lower scores indicating improvement over time. Scores ranging from 1-3 indicate improvement. Only patients that demonstrated improvement at week 12 were reported; scores for earlier weeks were only used to assess progress throughout the study.
Outcome measures
| Measure |
Lithium Treatment Group
n=38 Participants
The patient will be started on lithium 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on lithium blood level. Blood will be drawn at each study visit. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Lithium
|
Placebo Group
n=39 Participants
The patient will be started on placebo 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on sham lithium blood level. Blood will be drawn for sham lithium levels at weeks 2, 4, 6, 8, and 12. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Placebo
|
|---|---|---|
|
Clinical Global Impression (CGI) Behavior Change
|
12 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: Assessed at Week 0, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12Young Mania Rating Scale total score is the measure used to assess symptoms that occur in mania; each item is a symptom that is rated for severity. Scoring range 0-60. Minimum score is 0 and maximum score is 60. Higher scores mean a worse outcome.
Outcome measures
| Measure |
Lithium Treatment Group
n=38 Participants
The patient will be started on lithium 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on lithium blood level. Blood will be drawn at each study visit. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Lithium
|
Placebo Group
n=39 Participants
The patient will be started on placebo 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on sham lithium blood level. Blood will be drawn for sham lithium levels at weeks 2, 4, 6, 8, and 12. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Placebo
|
|---|---|---|
|
Young Mania Rating Scale
|
3.1 score on a scale
Interval 0.9 to 5.3
|
1.1 score on a scale
Interval -1.1 to 3.3
|
SECONDARY outcome
Timeframe: Assessed at Week 0, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12Treatment Emergent Symptom Scale that covers 26 somatic symptoms, each rated as present (score=1) or absent (score=0). Total score is the measure used with scoring range 0-26; higher scores indicate more somatic symptoms.
Outcome measures
| Measure |
Lithium Treatment Group
n=38 Participants
The patient will be started on lithium 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on lithium blood level. Blood will be drawn at each study visit. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Lithium
|
Placebo Group
n=39 Participants
The patient will be started on placebo 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on sham lithium blood level. Blood will be drawn for sham lithium levels at weeks 2, 4, 6, 8, and 12. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Placebo
|
|---|---|---|
|
Treatment Emergent Signs and Symptoms
|
0.6 score on a scale
Interval -1.3 to 2.4
|
0.7 score on a scale
Interval -1.1 to 2.5
|
SECONDARY outcome
Timeframe: Assessed at Week 0, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12Simpson Angus Scale for Extrapyramidal Sign requires in-person examination to assess gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head dropping, glabella tap, tremor, and salivation. Total score is the measure used, range 0-40; higher scores indicate increased severity of signs.
Outcome measures
| Measure |
Lithium Treatment Group
n=38 Participants
The patient will be started on lithium 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on lithium blood level. Blood will be drawn at each study visit. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Lithium
|
Placebo Group
n=39 Participants
The patient will be started on placebo 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on sham lithium blood level. Blood will be drawn for sham lithium levels at weeks 2, 4, 6, 8, and 12. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Placebo
|
|---|---|---|
|
Simpson-Angus Scale
|
-0.0 score on a scale
Interval -1.1 to 1.0
|
0.0 score on a scale
Interval -1.0 to 1.0
|
SECONDARY outcome
Timeframe: Assessed at Week 0, Week2, Week 4, Week 6, Week 8, Week 10, Week 12Basic Activities of Daily Living with items for 6 functions: bathing, dressing, toileting, transferring, continence, and feeding. Each item is scored as unimpaired=1, impaired=0. Total score is the measure used, range 0-6; higher scores indicate better functioning.
Outcome measures
| Measure |
Lithium Treatment Group
n=38 Participants
The patient will be started on lithium 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on lithium blood level. Blood will be drawn at each study visit. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Lithium
|
Placebo Group
n=39 Participants
The patient will be started on placebo 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on sham lithium blood level. Blood will be drawn for sham lithium levels at weeks 2, 4, 6, 8, and 12. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Placebo
|
|---|---|---|
|
Basic Activities of Daily Living (BADL)
|
0.3 score on a scale
Interval -0.1 to 0.7
|
0.1 score on a scale
Interval -0.3 to 0.6
|
SECONDARY outcome
Timeframe: Assessed at Week 0, Week 4, Week 8, Week 10, Week 12Zarit Caregiver Burden Interview with the caregiver asked to rank 22 items on a scale with responses for each item from 'never' (score 0) to 'nearly always' (score 4). Total score is the measure used; range 0-88 with higher scores indicating greater caregiver burden.
Outcome measures
| Measure |
Lithium Treatment Group
n=38 Participants
The patient will be started on lithium 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on lithium blood level. Blood will be drawn at each study visit. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Lithium
|
Placebo Group
n=39 Participants
The patient will be started on placebo 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on sham lithium blood level. Blood will be drawn for sham lithium levels at weeks 2, 4, 6, 8, and 12. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Placebo
|
|---|---|---|
|
Zarit Caregiver Burden Interview
|
2.8 score on a scale
Interval -1.1 to 6.6
|
-0.4 score on a scale
Interval -4.2 to 3.3
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Assessed at Screening, Week 1230 item questionnaire used to assess degree of cognitive impairment. Orientation, registration, attention/calculation, recall, language, repetitions and commands are assessed. Total score is the measure used; range 0-30, higher scores indicate better global cognitive function.
Outcome measures
| Measure |
Lithium Treatment Group
n=38 Participants
The patient will be started on lithium 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on lithium blood level. Blood will be drawn at each study visit. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Lithium
|
Placebo Group
n=39 Participants
The patient will be started on placebo 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on sham lithium blood level. Blood will be drawn for sham lithium levels at weeks 2, 4, 6, 8, and 12. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Placebo
|
|---|---|---|
|
Folstein Mini-Mental Status Exam
|
0.9 score on a scale
Interval -0.3 to 2.2
|
0.9 score on a scale
Interval -0.4 to 2.1
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Assessed at Week 0, Week 12Neuropsychological test used to assess a patient's cognitive ability. The patient is asked to complete small tasks such as drawing shapes and printing their name. They are also asked to remember certain names and objects, such as a cup and a spoon, and the evaluator's first name. Total score is the measure used; range 0-100, higher scores indicate better cognition.
Outcome measures
| Measure |
Lithium Treatment Group
n=38 Participants
The patient will be started on lithium 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on lithium blood level. Blood will be drawn at each study visit. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Lithium
|
Placebo Group
n=39 Participants
The patient will be started on placebo 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on sham lithium blood level. Blood will be drawn for sham lithium levels at weeks 2, 4, 6, 8, and 12. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Placebo
|
|---|---|---|
|
Severe Impairment Battery
|
2.1 score on a scale
Interval -1.1 to 5.4
|
-0.0 score on a scale
Interval -3.3 to 3.2
|
Adverse Events
Lithium Treatment Group
Serious events: 11 serious events
Other events: 30 other events
Deaths: 0 deaths
Placebo Group
Serious events: 11 serious events
Other events: 33 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lithium Treatment Group
n=38 participants at risk
The patient will be started on lithium 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on lithium blood level. Blood will be drawn at each study visit. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Lithium
|
Placebo Group
n=39 participants at risk
The patient will be started on placebo 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on sham lithium blood level. Blood will be drawn for sham lithium levels at weeks 2, 4, 6, 8, and 12. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Placebo
|
|---|---|---|
|
Blood and lymphatic system disorders
Hypernatremia
|
2.6%
1/38 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
0.00%
0/39 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Psychiatric disorders
Altered Mental Status
|
2.6%
1/38 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
0.00%
0/39 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Psychiatric disorders
Increased Agitation
|
7.9%
3/38 • Number of events 3 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
12.8%
5/39 • Number of events 5 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Musculoskeletal and connective tissue disorders
Fall
|
5.3%
2/38 • Number of events 2 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
2.6%
1/39 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
5.3%
2/38 • Number of events 2 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
0.00%
0/39 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Endocrine disorders
Hypoglycemia
|
2.6%
1/38 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
0.00%
0/39 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
General disorders
Dehydration
|
2.6%
1/38 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
0.00%
0/39 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Renal and urinary disorders
Urinary Tract Infection
|
0.00%
0/38 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
2.6%
1/39 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Tract Infection
|
0.00%
0/38 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
2.6%
1/39 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Gastrointestinal disorders
Stomach Infection
|
0.00%
0/38 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
2.6%
1/39 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Blood and lymphatic system disorders
Hyponatremia
|
0.00%
0/38 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
2.6%
1/39 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Musculoskeletal and connective tissue disorders
Myoclonus
|
0.00%
0/38 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
2.6%
1/39 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
Other adverse events
| Measure |
Lithium Treatment Group
n=38 participants at risk
The patient will be started on lithium 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on lithium blood level. Blood will be drawn at each study visit. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Lithium
|
Placebo Group
n=39 participants at risk
The patient will be started on placebo 150mg/day, with subsequent dose titration to 300mg/day at the 2-week visit, 450mg/day at the 4-week visit, and 600mg/day (maximum daily dose) if tolerated and based on sham lithium blood level. Blood will be drawn for sham lithium levels at weeks 2, 4, 6, 8, and 12. This upward dose titration will occur only if clinically indicated (absence of response at lower doses without intolerable side effects).
Patients who develop side effects, e.g., tremor, falls, will have their dose reduced.
Placebo
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
5.3%
2/38 • Number of events 2 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
0.00%
0/39 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Skin and subcutaneous tissue disorders
Contact Dermatitis
|
2.6%
1/38 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
2.6%
1/39 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Nervous system disorders
Headache
|
2.6%
1/38 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
2.6%
1/39 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Psychiatric disorders
Increased Anxiety
|
5.3%
2/38 • Number of events 2 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
0.00%
0/39 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Psychiatric disorders
Increased Agitation
|
15.8%
6/38 • Number of events 6 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
28.2%
11/39 • Number of events 11 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Musculoskeletal and connective tissue disorders
Fall
|
18.4%
7/38 • Number of events 7 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
7.7%
3/39 • Number of events 3 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Gastrointestinal disorders
Diarrhea
|
7.9%
3/38 • Number of events 3 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
10.3%
4/39 • Number of events 4 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Renal and urinary disorders
Reduced Kidney Function
|
7.9%
3/38 • Number of events 3 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
5.1%
2/39 • Number of events 2 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Gastrointestinal disorders
Vomiting
|
10.5%
4/38 • Number of events 4 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
2.6%
1/39 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Nervous system disorders
Gait Instability
|
10.5%
4/38 • Number of events 4 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
0.00%
0/39 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Renal and urinary disorders
Urinary Tract Infection
|
5.3%
2/38 • Number of events 2 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
5.1%
2/39 • Number of events 2 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Psychiatric disorders
Insomnia
|
5.3%
2/38 • Number of events 2 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
2.6%
1/39 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
5.3%
2/38 • Number of events 2 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
2.6%
1/39 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Nervous system disorders
Tremor
|
7.9%
3/38 • Number of events 3 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
0.00%
0/39 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Psychiatric disorders
Increased Confusion
|
2.6%
1/38 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
2.6%
1/39 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Musculoskeletal and connective tissue disorders
Muscle Pain
|
0.00%
0/38 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
5.1%
2/39 • Number of events 2 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Nervous system disorders
Myoclonus
|
2.6%
1/38 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
2.6%
1/39 • Number of events 1 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
|
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Tract Infection
|
0.00%
0/38 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
5.1%
2/39 • Number of events 2 • 12 weeks.
Adverse events were based on self-report and caregiver report. Treatment Emergent Symptom Scale (TESS) total score was the measure for somatic side effects.
|
Additional Information
Davangere Devanand, MD
New York State Psychiatric Institute
Phone: 646.774.8656
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place