Trial Outcomes & Findings for Cost- Effectiveness and Quality of Life Assessment in Mood Disorder (NCT NCT02870283)
NCT ID: NCT02870283
Last Updated: 2020-11-20
Results Overview
Response to treatment was defined as a 50% reduction from baseline scores in Hamilton Rating Scale for Depression (HRSD)and Young Mania Rating Scale (YMRS) scales HRSD was developed to evaluate and quantify depression.Its abbreviated version,. Scoring is based on the 17-item scale and scores of 0-7 are considered as being normal. The cutoff points are: 8-17 for mild depression,18-24 for moderate depression, and 25 or more for severe depression. The maximum score being 52 on the 17-point scale. YMRS is is the most widely used assessment tool for manic symptoms. The scale consists of 11 items .The YMRS follows the style of the Hamilton Rating Scale for Depression (HAM-D) with each item given a severity rating. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/agressive behavior), while the remaining seven items are graded on a 0 to 4 scale. Scores of YMRS \> 20 generates indicate mania
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
107 participants
Primary outcome timeframe
8 weeks
Results posted on
2020-11-20
Participant Flow
Response to treatment was assessed for the entire algorithm. There were no comparisons between the steps of each arm of the study
Participant milestones
| Measure |
Lithium
Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine).
Group (A) Started Lithium (900mg-1500mg)
Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks.
1. First step: Monotherapy with Lithium (900-1500mg) Non responsive patients: 2nd step.
2. Second step: Randomization for lithium (900mg-1500mg) + valproic acid (1000mg-1500mg) OR lithium (900mg-1500mg) + carbamazepine (600mg-1200mg).
Non responsive patients: 3rd step.
3. Third step: Crossover lithium (900mg-1500mg) + valproic acid (1000mg-1500mg) X lithium (900mg-1500mg) + carbamazepine (600mg-1200mg).
Non responsive patients: 4th step.
4. Fourth step: Association with risperidone (1-6mg)
Lithium
|
Acid Valproic
Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine).
Group (B) Started Valproic Acid (1000mg-1500mg).
Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks.
1. First step: Monotherapy with Valproic Acid (1000mg-1500mg) Non responsive patients: 2nd step.
2. Second step: Association with lithium (900mg-1500mg). Non responsive patients: 3rd step.
3. Third step: Crossover: lithium (900mg-1500mg) + carbamazepine (600mg-1200mg). Non responsive patients: 4th step.
4. Fourth step: Association with risperidone (1-6mg)
Valproic Acid
|
Carbamazepine
Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine).
Group (C) Started Carbamazepine (600mg-1200mg).
Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks.
1. First step: Monotherapy with Carbamazepine (600mg-1200mg). Non responsive patients: 2nd step.
2. Second step: Association with lithium (900mg-1500mg). Non responsive patients: 3rd step.
3. Third step: Crossover: lithium (900mg-1500mg) + valproic acid (1000mg-1500mg). Non responsive patients: 4th step.
4. Fourth step: Association with risperidone (1-6mg)
Carbamazepine
|
|---|---|---|---|
|
Overall Study
STARTED
|
38
|
35
|
34
|
|
Overall Study
COMPLETED
|
35
|
26
|
15
|
|
Overall Study
NOT COMPLETED
|
3
|
9
|
19
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Cost- Effectiveness and Quality of Life Assessment in Mood Disorder
Baseline characteristics by cohort
| Measure |
Lithium
n=38 Participants
Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine).
Group (A) Started Lithium (900mg-1500mg)
Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks.
1. First step: Monotherapy with Lithium (900-1500mg) Non responsive patients: 2nd step.
2. Second step: Randomization for lithium (900mg-1500mg) + valproic acid (1000mg-1500mg) OR lithium (900mg-1500mg) + carbamazepine (600mg-1200mg).
Non responsive patients: 3rd step.
3. Third step: Crossover lithium (900mg-1500mg) + valproic acid (1000mg-1500mg) X lithium (900mg-1500mg) + carbamazepine (600mg-1200mg).
Non responsive patients: 4th step.
4. Fourth step: Association with risperidone (1-6mg)
Lithium
|
Acid Valproic
n=35 Participants
Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine).
Group (B) Started Valproic Acid (1000mg-1500mg).
Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks.
1. First step: Monotherapy with Valproic Acid (1000mg-1500mg) Non responsive patients: 2nd step.
2. Second step: Association with lithium (900mg-1500mg). Non responsive patients: 3rd step.
3. Third step: Crossover: lithium (900mg-1500mg) + carbamazepine (600mg-1200mg). Non responsive patients: 4th step.
4. Fourth step: Association with risperidone (1-6mg)
Valproic Acid
|
Carbamazepine
n=34 Participants
Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine).
Group (C) Started Carbamazepine (600mg-1200mg).
Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks.
1. First step: Monotherapy with Carbamazepine (600mg-1200mg). Non responsive patients: 2nd step.
2. Second step: Association with lithium (900mg-1500mg). Non responsive patients: 3rd step.
3. Third step: Crossover: lithium (900mg-1500mg) + valproic acid (1000mg-1500mg). Non responsive patients: 4th step.
4. Fourth step: Association with risperidone (1-6mg)
Carbamazepine
|
Total
n=107 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
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
38 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
107 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Continuous
|
43.6 years
STANDARD_DEVIATION 13.17 • n=5 Participants
|
43.6 years
STANDARD_DEVIATION 13.17 • n=7 Participants
|
43.6 years
STANDARD_DEVIATION 13.17 • n=5 Participants
|
43.6 years
STANDARD_DEVIATION 13.17 • n=4 Participants
|
|
Sex: Female, Male
Female
|
31 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
86 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
|
Region of Enrollment
Brazil
|
38 participants
n=5 Participants
|
35 participants
n=7 Participants
|
34 participants
n=5 Participants
|
107 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 8 weeksResponse to treatment was defined as a 50% reduction from baseline scores in Hamilton Rating Scale for Depression (HRSD)and Young Mania Rating Scale (YMRS) scales HRSD was developed to evaluate and quantify depression.Its abbreviated version,. Scoring is based on the 17-item scale and scores of 0-7 are considered as being normal. The cutoff points are: 8-17 for mild depression,18-24 for moderate depression, and 25 or more for severe depression. The maximum score being 52 on the 17-point scale. YMRS is is the most widely used assessment tool for manic symptoms. The scale consists of 11 items .The YMRS follows the style of the Hamilton Rating Scale for Depression (HAM-D) with each item given a severity rating. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/agressive behavior), while the remaining seven items are graded on a 0 to 4 scale. Scores of YMRS \> 20 generates indicate mania
Outcome measures
| Measure |
Lithium
n=38 Participants
Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine).
Group (A) Started Lithium (900mg-1500mg)
Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks.
1. First step: Monotherapy with Lithium (900-1500mg) Non responsive patients: 2nd step.
2. Second step: Randomization for lithium (900mg-1500mg) + valproic acid (1000mg-1500mg) OR lithium (900mg-1500mg) + carbamazepine (600mg-1200mg).
Non responsive patients: 3rd step.
3. Third step: Crossover lithium (900mg-1500mg) + valproic acid (1000mg-1500mg) X lithium (900mg-1500mg) + carbamazepine (600mg-1200mg).
Non responsive patients: 4th step.
4. Fourth step: Association with risperidone (1-6mg)
Lithium
|
Acid Valproic
n=35 Participants
Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine).
Group (B) Started Valproic Acid (1000mg-1500mg).
Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks.
1. First step: Monotherapy with Valproic Acid (1000mg-1500mg) Non responsive patients: 2nd step.
2. Second step: Association with lithium (900mg-1500mg). Non responsive patients: 3rd step.
3. Third step: Crossover: lithium (900mg-1500mg) + carbamazepine (600mg-1200mg). Non responsive patients: 4th step.
4. Fourth step: Association with risperidone (1-6mg)
Valproic Acid
|
Carbamazepine
n=34 Participants
Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine).
Group (C) Started Carbamazepine (600mg-1200mg).
Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks.
1. First step: Monotherapy with Carbamazepine (600mg-1200mg). Non responsive patients: 2nd step.
2. Second step: Association with lithium (900mg-1500mg). Non responsive patients: 3rd step.
3. Third step: Crossover: lithium (900mg-1500mg) + valproic acid (1000mg-1500mg). Non responsive patients: 4th step.
4. Fourth step: Association with risperidone (1-6mg)
Carbamazepine
|
|---|---|---|---|
|
Number of Participants With Response to Treatment"
|
31 Participants
|
28 Participants
|
27 Participants
|
SECONDARY outcome
Timeframe: 8 monthsThe remission outcome was established as obtaining three consecutive visits with scores of values considered asymptomatic Hamilton Rating Scale for Depression(HRSD \<7 points) and Young Mania Rating Scale (YMRS \<6 points) during the trial. The subjects that were asymptomatic for at least 6-8 month were considered to be in partial remission and complete if at least 12 months without symptoms, according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).
Outcome measures
| Measure |
Lithium
n=38 Participants
Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine).
Group (A) Started Lithium (900mg-1500mg)
Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks.
1. First step: Monotherapy with Lithium (900-1500mg) Non responsive patients: 2nd step.
2. Second step: Randomization for lithium (900mg-1500mg) + valproic acid (1000mg-1500mg) OR lithium (900mg-1500mg) + carbamazepine (600mg-1200mg).
Non responsive patients: 3rd step.
3. Third step: Crossover lithium (900mg-1500mg) + valproic acid (1000mg-1500mg) X lithium (900mg-1500mg) + carbamazepine (600mg-1200mg).
Non responsive patients: 4th step.
4. Fourth step: Association with risperidone (1-6mg)
Lithium
|
Acid Valproic
n=35 Participants
Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine).
Group (B) Started Valproic Acid (1000mg-1500mg).
Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks.
1. First step: Monotherapy with Valproic Acid (1000mg-1500mg) Non responsive patients: 2nd step.
2. Second step: Association with lithium (900mg-1500mg). Non responsive patients: 3rd step.
3. Third step: Crossover: lithium (900mg-1500mg) + carbamazepine (600mg-1200mg). Non responsive patients: 4th step.
4. Fourth step: Association with risperidone (1-6mg)
Valproic Acid
|
Carbamazepine
n=34 Participants
Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine).
Group (C) Started Carbamazepine (600mg-1200mg).
Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks.
1. First step: Monotherapy with Carbamazepine (600mg-1200mg). Non responsive patients: 2nd step.
2. Second step: Association with lithium (900mg-1500mg). Non responsive patients: 3rd step.
3. Third step: Crossover: lithium (900mg-1500mg) + valproic acid (1000mg-1500mg). Non responsive patients: 4th step.
4. Fourth step: Association with risperidone (1-6mg)
Carbamazepine
|
|---|---|---|---|
|
Number of Participants With Remission to Treatment
|
10 Participants
|
9 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: 12 weeksQuality of Life - WHOQOL -BREF instrument scores scores 0-20 . higher scores mean a better outcome. The quality of life was assessed for entire algorithm. There were no comparisons between each arms of the study.
Outcome measures
| Measure |
Lithium
n=35 Participants
Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine).
Group (A) Started Lithium (900mg-1500mg)
Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks.
1. First step: Monotherapy with Lithium (900-1500mg) Non responsive patients: 2nd step.
2. Second step: Randomization for lithium (900mg-1500mg) + valproic acid (1000mg-1500mg) OR lithium (900mg-1500mg) + carbamazepine (600mg-1200mg).
Non responsive patients: 3rd step.
3. Third step: Crossover lithium (900mg-1500mg) + valproic acid (1000mg-1500mg) X lithium (900mg-1500mg) + carbamazepine (600mg-1200mg).
Non responsive patients: 4th step.
4. Fourth step: Association with risperidone (1-6mg)
Lithium
|
Acid Valproic
n=26 Participants
Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine).
Group (B) Started Valproic Acid (1000mg-1500mg).
Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks.
1. First step: Monotherapy with Valproic Acid (1000mg-1500mg) Non responsive patients: 2nd step.
2. Second step: Association with lithium (900mg-1500mg). Non responsive patients: 3rd step.
3. Third step: Crossover: lithium (900mg-1500mg) + carbamazepine (600mg-1200mg). Non responsive patients: 4th step.
4. Fourth step: Association with risperidone (1-6mg)
Valproic Acid
|
Carbamazepine
n=15 Participants
Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine).
Group (C) Started Carbamazepine (600mg-1200mg).
Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks.
1. First step: Monotherapy with Carbamazepine (600mg-1200mg). Non responsive patients: 2nd step.
2. Second step: Association with lithium (900mg-1500mg). Non responsive patients: 3rd step.
3. Third step: Crossover: lithium (900mg-1500mg) + valproic acid (1000mg-1500mg). Non responsive patients: 4th step.
4. Fourth step: Association with risperidone (1-6mg)
Carbamazepine
|
|---|---|---|---|
|
Quality of Life - WHOQOL Bref Intrument
|
10.91 score on a scale
Standard Deviation 3.44
|
10.91 score on a scale
Standard Deviation 3.44
|
10.91 score on a scale
Standard Deviation 3.44
|
Adverse Events
Lithium
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Acid Valproic
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Carbamazepine
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Dra. Ana Flávia Silva Lima
Universidade Federal do Rio Grande do Sul
Phone: +5551999185180
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place